Core C: Project Summary/Abstract Transplantation of hematopoietic stem and progenitor cells (HSPCs) underlies the only known case of HIV-1 functional cure. Over 12 years after this pioneering clinical case study, however, substantial improvements are needed in order to apply this case study to a broader spectrum of HIV+ individuals. The overarching goal of our U19 consortium is to identify candidate strategies to safely and effectively modify a patient's own HSPCs to resist HIV infection, and simultaneously enhance their ability to recognize and destroy infected cells. The Nonhuman Primate (NHP) Core will play a central role in organizing preclinical aspects of the approaches proposed by each project in our group, maintaining a focus on translationally relevant features that are best suited for future trials in patients. In Project 1 (Kitchen), we will generate a series of 12 NHPs that are transplanted with autologous, gene-modified HSPCs. These cells will express a promising virus-specific immune effector molecule known as CD4CAR, in combination with other promising therapies such as broadly neutralizing antibodies (bNAbs), and therapeutic vaccination. CD4CAR-modified HSPC progeny, in combination with bNAbs and vaccine-specific cells, represent a formidable and synergistic approach to target virus persistence. In Project 2 (Morizono), we will focus on approaches to gene-modify HSPCs without removing them from the body, studying a total of 9 NHP. So-called ?in vivo delivery? approaches will significantly enhance the applicability of anti-HIV gene therapies to patients around the world. In Project 3 (An), we will test another important aspect in a total of 6 NHP: the ability to precisely regulate the levels of gene-modified HSPCs and their progeny ex vivo and in vivo. Each of the NHP Core's project-specific functions will be assessed with an eye towards the clinic, in close consultation with our longstanding partners in Project 4 (Symonds). The goals set forth by the NHP Core are to implement each of the NHP studies described above, produce gene-modified NHP HSPC products using potent lentiviral vectors, and to provide supportive care for animals in each project, both following HSPC gene therapy and infection with HIV-like viruses. Each of the four projects in our consortium are highly complementary. We will bridge large animal studies overseen by each project, contribute meaningfully to discussions regarding synergies between projects, and evaluate new and promising therapies as they emerge.